Randomised clinical trial of the effects of prolonged-release melatonin, temazepam and zolpidem on slow-wave activity during sleep in healthy people

16 healthy adults aged 55-64 (12 men, 4 women; BMI 25.6; 14 White, 2 Black) participated in a randomized, double-blind, placebo-controlled four-treatment-night study with washouts; sleep assessed by polysomnography and EEG spectral analysis.

Prolonged-release melatonin 2 mg at 21:00; temazepam 20 mg at 22:45; zolpidem 10 mg at 22:45; placebo matched for each; single-dose per treatment night; four treatment nights with washouts of at least 5 days between treatments.

Melatonin 2 mg produced no significant change in nocturnal SWA across the night and did not meaningfully alter PSG measures or morning sleepiness; SWA decreased only in the first third of the night. Temazepam 20 mg and zolpidem 10 mg reduced SWA vs placebo, with temazepam showing stronger effects; zolpidem also reduced SWA in the 1.25–5.0 Hz band. Temazepam and zolpidem improved PSG measures (increases in total sleep time, NREM sleep duration, and sleep efficiency; reduced WASO; zolpidem increased REM latency). Subjective sleep quality improved with temazepam and zolpidem; melatonin did not. The different EEG effects reflect distinct mechanisms of action. The lack of major EEG effects with melatonin aligns with a relatively safe EEG profile and supports exploration in insomnia patients, though melatonin’s EEG impact appears limited in healthy older adults without melatonin deficiency.

Small sample (n=16) of healthy older adults; single-dose, short-term exposure; results may not generalize to younger individuals or to those with insomnia; some EEG data were excluded due to artefacts; secondary/exploratory endpoints had no multiplicity adjustment.